Preventive effect of antioxidants in MPTP-induced mouse model of Parkinson's disease

Neurosci Lett. 2004 Jun 17;363(3):243-6. doi: 10.1016/j.neulet.2004.03.072.

Abstract

Oxidative stress to dopaminergic neurons is believed to be one of the causes of neurodegeneration in Parkinson's disease (PD). It was investigated whether N-acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) have a preventive effect in an oxidative stress-induced model of PD. We found that NAC and OTC prevent degradation of PARP during auto-oxidized dopamine- or auto-oxidized L-DOPA-induced apoptosis in PC12 cells. In an animal model study, NAC and OTC showed a preventive effect against MPTP-induced loss of tyrosine hydroxylase-positive neurons, and suppressed the nuclear translocation of c-jun N-terminal kinase (JNK), suggesting that NAC and OTC can prevent MPTP-induced apoptosis by suppressing JNK activation. Therefore, these results suggest that NAC and OTC can be used as potential agents to prevent the progression of PD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Analysis of Variance
  • Animals
  • Antioxidants / therapeutic use*
  • Blotting, Western / methods
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cell Count
  • Cell Death / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Agents / toxicity
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Immunohistochemistry / methods
  • JNK Mitogen-Activated Protein Kinases
  • MPTP Poisoning / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • PC12 Cells
  • Pyrrolidonecarboxylic Acid
  • Rats
  • Thiazoles / therapeutic use*
  • Thiazolidines
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Antioxidants
  • Dopamine Agents
  • Thiazoles
  • Thiazolidines
  • Tyrosine 3-Monooxygenase
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Pyrrolidonecarboxylic Acid
  • Dopamine
  • Acetylcysteine
  • 2-oxothiazolidine-4-carboxylic acid